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Guidance on Safe Switching of Warfarin to DOAC

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Guidance on Safe Switching of Warfarin to DOAC Guidance for the safe switching of warfarin to direct oral anticoagulants (DOACs) for patients with non-valvular AF and venous thromboembolism (DVT / PE) during the coronavirus pandemic 26 March 2020 Lead Author: Helen Williams, FFRPS, FRPharmS Consultant Pharmacist for CVD, NHS Southwark CCG National Clinical Adviser for AF, AHSNs Network Endorsed by: Royal College of General Practitioners, British Haematology Society Guidance for the Safe Switching of Warfarin to Direct Oral Anticoagulants (DOACs) for Patients with Non-Valvular AF and Venous Thromboembolism (DVT / PE) Switching appropriate patients from warfarin to a DOAC may be considered to avoid regular blood tests for INR monitoring. Whilst DOACs require blood tests to assess renal function throughout treatment– the monitoring is predictable, less rigorous than INR testing with warfarin and is routinely carried out in primary care. Switching from warfarin to a DOAC must be done with careful consideration as not all patients are suitable for a switch to DOAC, and in some cases, specialist advice may be required. Patients should only be switched from warfarin to a DOAC by clinicians in primary or secondary care with experience in managing anticoagulation. To protect the supply chain for all patients – take a phased approach over the 12-week cycle of INR monitoring. Consider prioritising patients with poor control of INR as this cohort will require the most frequent INR checks. Address non-adherence if this an underlying reason for poor INR control. All DOACs are licensed for the prevention of atrial fibrillation (AF)-related stroke in people with non-valvular AF and for the treatment and secondary prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE). Is anticoagulation still required? For example, can anticoagulant therapy be stopped in patients with prior DVT / PE, where the risk of recurrence is now considered low – seek specialist advice if necessary Is a switch to a DOAC appropriate? A switch from warfarin to a DOAC should not be considered for patients: With a prosthetic mechanical valve With moderate to severe mitral stenosis With antiphospholipid antibody syndrome (APLS) Who are pregnant, breastfeeding or planning a pregnancy Requiring a higher INR than the standard INR range of 2.0 – 3.0 With severe renal impairment - Creatinine Clearance (CrCl) < 15ml/min With active malignancy/ chemotherapy (unless advised by a specialist) Prescribed interacting drugs – check SPCs (links below) for full list o Some HIV antiretrovirals and hepatitis antivirals - check with HIV drug interactions website at https://www.hiv-druginteractions.org/ o Some antiepileptics- phenytoin, carbamazepine, phenobarbitone or rifampicin are likely to reduce DOAC levels so should be discussed with an anticoagulation specialist On triple therapy (dual antiplatelet therapy plus warfarin) without discussing with an anticoagulant specialist or cardiologist There is little data on DOACs for patients with venous thrombosis at unusual sites (e.g. portal vein thrombosis) and these patients should be discussed with an anticoagulation specialist When switching to a DOAC, care should be taken to follow the recommendations in the relevant SPC: - Apixaban (Eliquis®) https://www.medicines.org.uk/emc/product/2878/smpc - Dabigatran (Pradaxa®) https://www.medicines.org.uk/emc/product/4703/smpc - Edoxaban (Lixiana®) https://www.medicines.org.uk/emc/product/6905/smpc - Rivaroxaban (Xarelto®) https://www.medicines.org.uk/emc/product/2793/smpc Choose DOAC drug and dose according to the therapeutic indication, patient age, actual bodyweight, renal function – calculated Creatinine Clearance (CrCl), drug interactions and patient preference/lifestyle (see table below) Guidance for the Safe Switching of Warfarin to Direct Oral Anticoagulants (DOACs) for Patients with Non-Valvular AF and Venous Thromboembolism (DVT / PE) - 26 March 2020 Guidance on DOAC Prescribing for Non-Valvular AF and DVT/PE DOAC Apixaban Edoxaban Rivaroxaban Dabigatran How to change from Stop warfarin. Start DOAC when INR ≤2.5 - See additional guidance overleaf warfarin (from EHRA guidance: https://academic.oup.com/eurheartj/article/39/16/1330/4942493?guestAccessKey=e7e62356-8aa6-472a-aeb1-eb5b58315d49) Baseline checks Renal function (CrCl)- serum creatinine (Cr) and bodyweight, full blood count (FBC), liver function tests (LFTs). Use results from last 3 months if stable. If for AF: CHA2DS2VASC and HASBLED scores. Dosing in Non- Prescribe Apixaban 5mg twice Prescribe Edoxaban 60mg once Prescribe Rivaroxaban 20mg once daily Prescribe Dabigatran 150mg twice daily if valvular AF daily daily aged <75 years, CrCl> 50mL/min, low risk of (lifelong unless bleeding (weight <50kg with close clinical risk:benefit of surveillance) anticoagulation therapy Reduce dose to 2.5mg twice daily Reduce dose to 30mg once daily Reduce dose to 15mg once daily if CrCl< Reduce dose to 110mg twice daily if aged > changes) if at least two of the following if: Body weight <61kg, or CrCl< 50mL/min in NVAF patients only. 80 years or prescribed verapamil. Consider characteristics: age ≥ 80 years, 50ml/min, or co-prescribed with 110mg twice daily based on individual body weight ≤ 60 kg, or serum ciclosporin, dronedarone, assessment of thrombotic risk and the risk creatinine ≥ 133 micromol/l or if erythromycin or ketoconazole. of bleeding in patients aged between 75 exclusive criteria of CrCl 15 - 29 and 80 years or with CrCl <50mL/min or ml/min. with increased risk of bleeding (including gastritis, oesophagitis, gastro-oesophageal reflux). Dosing in patients Dose is 5mg twice daily (use with Dosing as above. Dose is 20mg daily (consider 15mg dose Dosing as above. with DVT / PE caution if CrCl <30ml/min). Check Check intended duration of if CrCl<50ml/min and bleeding risk Check intended duration of therapy. (loading doses are not intended duration of therapy. therapy. outweighs VTE risk). required if patient has For long term prevention of Check intended duration of therapy. been stabilised on recurrence 2.5mg twice daily For long term prevention of recurrence warfarin) (after 6 months’ treatment dose). 10mg daily could be considered. Duration of therapy For a provoked DVT/PE: 3 months treatment if provoking factors have been addressed. for DVT/PE For unprovoked DVT/PE or recurrent DVT/PE: At least 6 months treatment dose followed by prophylaxis dosing as indicated/advised. Contraindications CrCl <15ml/min CrCl <15ml/min CrCl <15ml/min CrCl <30ml/min Cautions CrCl >95ml/min CrCl <30ml/min. Take with or after food Do not use in a standard medication See also individual SPCSs (15mg and 20mg doses). compliance aids (MCA) Interactions Ketoconazole, itraconazole, Rifampicin, phenytoin, Ketoconazole, itraconazole, Ketoconazole, ciclosporin, itraconazole, voriconazole, posaconazole, carbamazepine, phenobarbital or voriconazole, posaconazole, ritonavir, tacrolimus, dronedarone - contraindicated Check BNF: ritonavir - not recommended St. John's Wort – use with caution dronedarone – not recommended (See SPC for full details) www.bnf.org (See SPC for full details) Ciclosporin, dronedarone, (See SPC for full details) Rifampicin, St John’s Wort, carbamazepine, SPC: Rifampicin, phenytoin, erythromycin, ketoconazole – Rifampicin, phenytoin, carbamazepine, phenytoin –should be avoided. www.medicines.org.uk carbamazepine, phenobarbital, St. reduce dose as above. phenobarbital, St. John's Wort – Should Amiodarone, quinidine, ticagrelor, John's Wort – use with caution. (See BNF and SPC for edoxaban be avoided. posaconazole – use with caution. Do not use apixaban with patients for further information) Verapamil (use reduced dose). on strong enzyme inducers for Antidepressants: SSRIs and SNRIs- increased acute VTE treatment bleeding risk Guidance for the Safe Switching of Warfarin to Direct Oral Anticoagulants (DOACs) for Patients with Non-Valvular AF and Venous Thromboembolism (DVT / PE) - 26 March 2020 Pragmatic Approach to Stopping Warfarin and Starting DOAC in relation to the INR SPCs recommend different INRs at which to initiate DOACs after stopping warfarin: Apixaban and Dabigatran: Start when INR < 2 Edoxaban: Start when INR < 2.5 Rivaroxaban: Start when INR < 3 This approach would require repeat INR checks daily until the required INR is achieved. EHRA guidance gives pragmatic guidance on when to start DOACs after stopping warfarin: If INR < 2: Commence DOAC that day If INR between 2 and 2.5: Commence DOAC the next day (ideally) or the same day If INR between 2.5 and 3: Withhold warfarin for 24-48 hours and then initiate DOAC https://academic.oup.com/eurheartj/article/39/16/1330/4942493?guestAccessKey=e7e62356-8aa6-472a-aeb1-eb5b58315d49 Suggested process for safe switching from warfarin to a DOAC (Undertake steps remotely where possible) 1. Check clinical system for recent U&Es, LFTs and FBC (within last 3 months) 2. At next INR visit– check INR, record weight, take bloods if not already available or are unstable 3. Calculate creatinine clearance (CrCl) 4. Prescribe DOAC at appropriate dose and advise patient to obtain supplies 5. Advise patient when to stop warfarin in relation to starting DOAC (INR should be < 2.5 when DOAC is started) 6. Provide written instructions and involve family members / carers where possible to minimise the risk of patients taking both warfarin and the DOAC concurrently. Particular care should be taken where patients are using medication compliance aids to minimise the risk of incorrect dosing 7. Provide an up-to-date Anticoagulant Alert
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